Diisopropylamine → 1h-Pyrrolo[2,3-c]pyridine-2-methanol,a-2-pyridinyl-

HRID 1821894ノート

反応式

HRID 1821894 の反応式
C(NC(C)C)(C)C.C([Li])CCC.C1(S([N:22]2[C:26]3=[CH:27][N:28]=[CH:29][CH:30]=[C:25]3[CH:24]=[CH:23]2)(=O)=O)C=CC=CC=1.CN(C)CCN(C)C.[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH:45]=[O:46].[Cl-].[NH4+]>O1CCCC1>[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH:45]([C:23]1[NH:22][C:26]2=[CH:27][N:28]=[CH:29][CH:30]=[C:25]2[CH:24]=1)[OH:46]

参加物

8

反応物 6

HCID 7912DiisopropylamineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 142732-PyridinecarboxaldehydeHCID 25517Ammonium ChlorideHCID 595812711-(Phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridineHCID 178418339Butyllithium

生成物 1

HCID 578934801h-Pyrrolo[2,3-c]pyridine-2-methanol,a-2-pyridinyl-収率 19.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

A solution of diisopropylamine (0.43 mL, 3.07 mmol) in tetrahydrofuran (4 mL) was cooled to −78° C. under a nitrogen atmosphere. n-Butyllithium (1.24 mL of a 2.5 M solution in hexanes) was added dropwise and the reaction mixture was stirred for 30 min at −78° C. and then warmed to −30° C. A solution of 1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (Reference Example 12) (400 mg, 1.55 mmol) and N,N,N′,N′-tetramethylethylenediamine (0.24 mL, 1.59=mmol) in tetrahydrofuran (4 mL) was added and the reaction mixture was stirred for 30 min. A solution of 2-pyridinecarboxaldehyde (0.30 mL, 3.14 mmol) in tetrahydrofuran (3 mL) was added dropwise at −30° C. The reaction mixture was allowed to warm to ambient temperature over 1.5 h. Saturated ammonium chloride solution (7 mL) was added to quench the reaction mixture. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed successively with water and brine, dried over sodium sulfate and concentrated to dryness. Purification by Biotage chromotography (silica, 2 to 18% methanol in methylene chloride) produced (pyridin-2-yl)(1H-pyrrolo[2,3-c]pyridin-2-yl)methanol (67 mg, 12%) as an off-white solid: mp 166-169° C.; 1H NMR (500 MHz, CD3OD) δ6.05 (1H, s), 6.39 (1H, s), 7.34-7.36 (1H, m), 7.50-7.52 (1H, m), 7.72 (1H, d, J=7.9 Hz), 7.87 (1H, d, J=6.0 Hz), 8.00 (1H, d, J=5.6 Hz), 8.52 (1H, d, J=4.8 Hz), 8.62 (1H, s); ESI MS m/z 226 [C13H11N3O+H]+; HPLC (Method A) 98.9% (AUC), tR=13.1 min.

後処理

  1. temperaturewarmed to −30° C
  2. stirringthe reaction mixture was stirred for 30 min
  3. temperatureto warm to ambient temperature over 1.5 h
  4. customto quench the reaction mixture
  5. additionThe reaction mixture was diluted with water (10 mL)
  6. extractionextracted with ethyl acetate (2×25 mL)
  7. washThe combined organic extracts were washed successively with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness
  10. customPurification by Biotage chromotography (silica, 2 to 18% methanol in methylene chloride)

出典と根拠

ORDレコード
ord-2a16104e1e6346e092b42470b38421c9
出典データセット
uspto-grants-2009_10
特許番号
US07608627B2

反応ノート

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